Pharmaceutical dosage form comprising one or more antiretroviral active ingredients

Abstract

The invention relates to a pharmaceutical dosage form comprising one or more antiretroviral active ingredients in the form of a solid dispersion or solid solution in a matrix, wherein said matrix comprises an amino(meth)acrylate copolymer, characterized in that the matrix does not contain any essential amounts of pharmaceutically acceptable surfactants with an HLB value from 12 to 18 and in that the matrix comprises a mono carboxylic acid or an alcohol with 12 to 22 carbon atoms or both.

1 . A pharmaceutical dosage form, comprising:
 an antiretroviral active ingredient in the form of a solid dispersion or solid solution in a matrix,   wherein the matrix comprises an amino(meth)acrylate copolymer, the matrix does not contain any essential amounts of a pharmaceutically acceptable surfactant having an HLB value from 12 to 18 and the matrix comprises a mono carboxylic acid comprising 12 to 22 carbon atoms, an alcohol comprising 12 to 22 carbon atoms, or a mixture thereof.   
     
     
         2 . The pharmaceutical dosage form of  claim 1 , wherein the active antiretroviral ingredient belongs to the BCS class III or to the BCS class IV. 
     
     
         3 . The pharmaceutical dosage form of  claim 1 , wherein the active antiretroviral substance is a proteinase inhibitor. 
     
     
         4 . The pharmaceutical dosage form of  claim 1 , wherein the active antiretroviral ingredient is lopinavir, ritonavir, amprenavir, saquinavir, or their corresponding pharmaceutically acceptable salts, enantiomers, derivatives, polymorphs, prodrugs, solvates, or hydrates or combinations thereof or mixtures of these active ingredients. 
     
     
         5 . The pharmaceutical dosage form  claim 1 , wherein the active antiretroviral ingredient comprises lopinavir and ritonavir. 
     
     
         6 . The pharmaceutical dosage form of  claim 1 , wherein the active antiretroviral ingredient is the state of an amorphous particulate state of a solid dispersion. 
     
     
         7 . The pharmaceutical dosage form of  claim 1 , wherein the amino(meth)acrylate copolymer is a copolymer comprising 30 to 80% by weight of a C 1 - to C 4 -alkyl ester of acrylic or methacrylic acid, and 70 to 20% by weight of an alkyl(meth)acrylate monomer comprising a tertiary amino group in the alkyl radical. 
     
     
         8 . The pharmaceutical dosage form of  claim 1 , wherein the amino(meth)acrylate copolymer is a copolymer comprising 20-30% by weight of methyl methacrylate, 20-30% by weight of butyl methacrylate) and 60-40% by weight of dimethyl amino ethyl methacrylate. 
     
     
         9 . The pharmaceutical dosage form  claim 1 , wherein the mono carboxylic acid comprising 12 to 22 carbon atoms is lauric acid, myristic acid, palmitic acid, margaric acid, stearic acid, arachidic acid, behenic acid, oleic acid, linoleic acid, linoleic acid, eleostearic acid, arachidonic acid, or any mixture thereof. 
     
     
         10 . The pharmaceutical dosage form of  claim 1 , wherein the alcohol comprising 12 to 22 carbon atoms is lauryl alcohol, myristyl alcohol, palmityl alcohol, margaryl alcohol, stearyl alcohol, arachidyl alcohol, behenyl alcohol, or any mixture thereof. 
     
     
         11 . The pharmaceutical dosage form of  claim 1 , further comprising:
 at least one pharmaceutically acceptable excipient selected from the group consisting of an antioxidant, a brightener, a flavouring agent, a flow aid, a fragrance, a glidant, a penetration-promoting agent, a pigment, a polymer which is not an amino(meth)acrylate copolymer, a pore-forming agent, and a stabilizer.   
     
     
         12 . The pharmaceutical dosage form of  claim 1 , comprising:
 5 to 25% by weight lopinavir;   1 to 10% by weight ritonavir;   5 to 20% by weight stearic acid;   50-80% by weight amino methacrylate copolymer (USP/NF); and   up to 20% by weight of a further pharmaceutically acceptable excipient,   wherein the components add up to 100%.   
     
     
         13 . The pharmaceutical dosage form of  claim 1 , comprising 15% or less of a chemical degradation product of an initially incorporated antiretroviral active ingredient. 
     
     
         14 . A process for producing the pharmaceutical dosage form of  claim 1 , the process comprising:
 melt extruding at a temperature from 50 to 180° C. i) the antiretroviral active ingredient, ii) the amino(meth)acrylate copolymer, and iii) the monocarboxylic acid comprising 12 to 22 carbon atoms, the alcohol comprising 12 to 22 carbon atoms, or a mixture thereof.